The aim of this project is to synthesize a series of (deoxy) nucleoside derivatives that will be tested as inhibitors of HIV- reverse transcriptase. The basic idea is to use nucleoside bases or (deoxy) nucleoside related compounds to confer site specificity on known toxiphoric molecular assemblies. We believe that two other benefits will accrue: (a) the (deoxy) nucleoside residue should facilitate the entry of the toxiphore into the cell and (b) the increase in lipophilicity generally conferred on the nucleoside by the toxiphore should increase the probability of penetration of the CNS a desireable feature in the case of HIV. The toxiphores that we plan to use have moderate chemical reactivity and should behave as suicide inhibitors of HIV-reverse transcriptase if the enzyme mistakenly utilizes them as substrates - a reasonable possibility since the substrate requirements for this enzyme do not appear to be of high specificity. The toxiphores that we plan to use have been selected from groups of substances known to be associated with cytotoxicity whereas the nucleoside-related components have been chosen largely based on their acceptability as substrates to HIV-reverse transcriptase.